I focus on integrating laboratory experiments with computational studies for drug delivery system (DDS) design. My research centers on delivery systems for biomolecules—such as growth factors, mesenchymal stem cell secretome, genes, and peptides—as well as natural therapeutics including curcumin, α-mangostin, brazilin, quercetin, and concentrated deep-sea minerals, with applications in diabetic wound healing and cancer therapy. The DDS platforms I develop are primarily based on lipid- and polymer-based systems, as well as their complexes. In parallel with my experimental work, I have a strong interest in coding and have been developing tools to support nanoparticle modeling and simulation.
Drug Delivery Systems (DDS) Polymer and Lipid-Based Nanocarriers Biomolecule and Natural Drug Delivery Experimental and Computational Bioengineering Nanoparticle Modeling and Simulation
Film-forming sprays offer many advantages compared to conventional topical preparations because they can provide uniform drug distribution and dose, increased bioavailability, lower incidence of irritation, continuous drug release, and accelerated wound healing through moisture control. Film-forming sprays consist of polymers and excipients that improve the characteristics of preparations and enhance the stability of active substances. Each type of polymer and excipient will produce films with different features. Therefore, the various types of polymers and excipients and their evaluation standards need to be examined for the development of a more optimal form of film-forming spray. The selected literature included research on polymers as film-forming matrices and the application of these sprays for medical purposes or for potential medical use. This article discusses the types and concentrations of polymers and excipients, sprayer types, evaluations, and critical parameters in determining the sprayability and film characteristics. The review concludes that both natural and synthetic polymers that have in situ film or viscoelastic properties can be used to optimise topical drug delivery.
Human epidermal growth factor (hEGF) has been known to have excellent wound-healing activity. However, direct application to the wound area can lead to low hEGF bioavailability due to protease enzymes or endocytosis. The use of liposomes as coatings and carriers can protect hEGF from degradation by enzymes, chemical reactions, and immune reactions. Sustained release using a matrix polymer can also keep the levels of hEGF in line with the treatment. Therefore, this study aimed to develop a film-forming spray of water-soluble chitosan (FFSWSC) containing hEGF-liposomes as a potential wound dressing. The hEGF-liposomes were prepared using the hydration film method, and the preparation of the FFSWSC was achieved by the ionic gelation method. The hydration film method produced hEGF-liposomes that were round and spread with a Z-average of 219.3 nm and encapsulation efficiency of 99.87%, whereas the film-forming solution, which provided good sprayability, had a formula containing 2% WSC and 3% propylene glycol with a viscosity, spray angle, droplet size, spray weight, and occlusion factor of 21.94 ± 0.05 mPa.s, 73.03 ± 1.28°, 54.25 ± 13.33 µm, 0.14 ± 0.00 g, and 14.57 ± 3.41%, respectively. The pH, viscosity, and particle size of the FFSWSC containing hEGF-liposomes were stable during storage for a month in a climatic chamber (40 ± 2 °C, RH 75 ± 5%). A wound healing activity test on mice revealed that hEGF-liposomes in FFSWSC accelerated wound closure significantly, with a complete wound closure on day 6. Based on the findings, we concluded that FFSWSC containing hEGF-liposomes has the potential to be used as a wound dressing.
Abstract The present study was aimed to develop silybin phytosome (SIBP) and evaluate its effectiveness against cerebral ischemia‐reperfusion (CIR) injury in rats. Initially, SIBP was prepared and characterized with Fourier transform‐infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Drug loading and entrapment efficiency of SIBP were also calculated. High‐performance liquid chromatography was used to carry out bioavailability studies of SIBP. Adult Wistar rats were divided randomly into five groups. The CIR injury was induced after 14 days of pretreatment by occlusion of bilateral common carotid arteries for 30 min followed by 4 h of reperfusion. Biochemical estimation, histopathological studies, and in silico studies were carried out. Bioavailability studies revealed that SIB concentration was increased to twofolds in SIBP‐treated rats. SIBP treatment significantly increases superoxide dismutase and glutathione levels while it decreases monoaldehyde, tumor necrosis factor‐α (TNF‐α), and interleukin 6 (IL‐6) levels in both the hippocampus and cortex of the SIBP‐treated CIR‐injured rats. Histopathological studies reveal SIBP treatment alleviates cortex cell death and arrangement of CA1 neurons in CIR‐injured rats. In silico studies against proteins (TNF‐α and IL‐6) involved in cerebral ischemia revealed that silybin (SIB) exhibits strong binding interaction with the target proteins when compared to thalidomide which was used as the positive control. Phytosome increase SIB bioavailability and SIBP treatment showed promising results when compared to treatment with SIB only. Based on our study, we conclude that phytosome is a suitable drug delivery agent to the brain for SIB as SIBP treatment was able to provide neuroprotective action against CIR injury.
Colorectal cancer is one of the most common cancer diseases with the increase of cases prevalence >5% every year. Multidrug resistance mechanisms and non-localized therapy become primary problems of chemotherapy drugs for curing colorectal cancer disease. Therefore, the enteric-coated nanoparticle system has been studied and proved to be able to resolve those problems with good performance for colorectal cancer. The highlight of our review aims to summarize and discuss the enteric-coated nanoparticle drug delivery system specific for colorectal cancer disease. The main and supporting literatures were collected from published research articles of journals indexed in Scopus and PubMed databases. In the oral route of administration, Eudragit pH-sensitive copolymer as a coating agent prevents the degradation of the nanoparticle system from the gastric fluid and releases drug to intestinal-colon track. Therefore, it provides a colon-specific targeting ability. Impressively, enteric-coated nanoparticles having a sustained release profile significantly increase the cytotoxic effect of chemotherapeutic drugs and achieve cell-specific target delivery. The enteric-coated nanoparticle drug delivery system represents an excellent modification to improve the effectiveness and performance of anticancer drugs for colorectal cancer disease in terms of the oral route of administration.
Mangosteen fruit has been widely consumed and used as a source of antioxidants, either in the form of fresh fruit or processed products. However, mangosteen peel only becomes industrial waste due to its bitter taste, low content solubility, and poor stability. Therefore, this study aimed to design mangosteen peel extract microcapsules (MPEMs) and tablets to overcome the challenges. The fluidized bed spray-drying method was used to develop MPEM, with hydroxypropyl methylcellulose (HPMC) as the core mixture and polyvinyl alcohol (PVA) as the coating agent. The obtained MPEM was spherical with a hollow surface and had a size of 411.2 µm. The flow rate and compressibility of MPEM increased significantly after granulation. A formula containing 5% w/w polyvinyl pyrrolidone K30 (PVP K30) as a binder had the best tablet characteristics, with a hardness of 87.8 ± 1.398 N, friability of 0.94%, and disintegration time of 25.75 ± 0.676 min. Microencapsulation of mangosteen peel extract maintains the stability of its compound (total phenolic and α-mangosteen) and its antioxidant activity (IC50) during the manufacturing process and a month of storage at IVB zone conditions. According to the findings, the microencapsulation is an effective technique for improving the solubility and antioxidant stability of mangosteen peel extract during manufacture and storage.
Coronavirus disease 2019 (COVID-19) is a global pandemic infecting the respiratory system through a notorious virus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to viral mutations and the risk of drug resistance, it is crucial to identify new molecules having potential prophylactic or therapeutic effect against SARS-CoV-2 infection. In the present study, we aimed to identify a potential inhibitor of SARS-CoV-2 through virtual screening of a compound library of 470 quercetin derivatives by targeting the main protease—Mpro (PDB ID: 6LU7). The study was carried out with computational techniques such as molecular docking simulation studies (MDSS), molecular dynamics (MD) simulations, and molecular mechanics generalized Born surface area (MMGBSA) techniques. Among the natural derivatives, compound 382 (PubChem CID 65604) showed the best binding affinity to Mpro (−11.1 kcal/mol). Compound 382 interacted with LYS5, TYR126, GLN127, LYS137, ASP289, PHE291, ARG131, SER139, GLU288, and GLU290 of the Mpro protein. The SARS-CoV-2 Mpro-382 complex showed acceptable stability during the 100 ns MD simulations. The SARS-CoV-2 Mpro-382 complex also showed an MM-GBSA binding free energy value of -54.0 kcal/mol. The binding affinity, stability, and free energy results for 382 and Mpro were better than those of the native ligand and the standard inhibitors ledipasvir and cobicistat. The conclusion of our study was that compound 382 has the potential to inhibit SARS-Cov-2 Mpro. However, further investigations such as in-vitro assays are recommended to confirm its in-silico potency.
Stem cells’ secretome contains biomolecules that are ready to give therapeutic activities. However, the biomolecules should not be administered directly because of their in vivo instability. They can be degraded by enzymes or seep into other tissues. There have been some advancements in localized and stabilized secretome delivery systems, which have increased their effectiveness. Fibrous, in situ, or viscoelastic hydrogel, sponge-scaffold, bead powder/ suspension, and bio-mimetic coating can maintain secretome retention in the target tissue and prolong the therapy by sustained release. Porosity, young’s modulus, surface charge, interfacial interaction, particle size, adhesiveness, water absorption ability, in situ gel/film, and viscoelasticity of the preparation significantly affect the quality, quantity, and efficacy of the secretome. Therefore, the dosage forms, base materials, and characteristics of each system need to be examined to develop a more optimal secretome delivery system. This article discusses the clinical obstacles and potential solutions for secretome delivery, characterization of delivery systems, and devices used or potentially used in secretome delivery for therapeutic applications. This article concludes that secretome delivery for various organ therapies necessitates the use of different delivery systems and bases. Coating, muco-, and cell-adhesive systems are required for systemic delivery and to prevent metabolism. The lyophilized form is required for inhalational delivery, and the lipophilic system can deliver secretomes across the blood-brain barrier. Nano-sized encapsulation and surface-modified systems can deliver secretome to the liver and kidney. These dosage forms can be administered using devices such as a sprayer, eye drop, inhaler, syringe, and implant to improve their efficacy through dosing, direct delivery to target tissues, preserving stability and sterility, and reducing the immune response.
Diabetes-related wounds have physiological factors that make healing more complicated. High sugar levels can increase microbial infection risk while limiting nutrition and oxygen transfer to the wound area. The secretome of mesenchymal stem cells has been widely known for its efficacy in regenerative therapy. However, applying the secretome directly to the wound can reduce its effectiveness. In this review, we examined the literature on synthesizing the combinations of carboxymethyl chitosan, hyaluronic acid, and collagen tripeptides, as well as the possibility of physicochemical properties enhancement of the hydrogel matrix, which could potentially be used as an optimal delivery system of stem cell’s secretome for diabetic wound healing.
Quercetin derivatives are known to have significant anticancer activity. The activity is strongly influenced by the type and position of the substituent group. By studying the structural pattern of quercetin and its impact on their binding affinity, the development of quercetin-based drugs can be optimized. The study aimed to determine the impact of 3D structure, type, and position of quercetin moiety on its activity against ROS-modulating enzymes that play a role in the induction and growth of ROS-induced cancer. The 23 natural quercetin derivatives were docked to 7 ROS-modulating enzymes using Autodock Vina to determine their binding affinity and interaction. The interaction stability was further studied through molecular dynamics simulation using the CABS Flex 2.0 server. Determination of crucial amino acid targets of the quercetin group was determined using DockFlin. Finally, the toxicity of each test ligand was determined using the pkCSM server. The highest binding affinity for SOD and NOX was produced by quercetin 3'-glucoside with the binding energy of -10.2 and -12.8 kcal/mol. Quercetin 3,4'-diglucoside had the highest binding affinity for CAT and GR at -11.5 and -10.5 kcal/mol, respectively. Routine produced the highest binding affinity at LOX (-10.9). Quercetin 3-O-xyloside and quercetin 3-O-rhamnoside-7-O-glucoside had the highest binding affinity in XO with a value of -10.4 kcal/mol. The glucose and prenyl groups are beneficial for quercetin in interacting with all ROS-modulating enzymes except XO. In contrast, the methoxy group negatively affects all interactions of quercetin with receptors. The perfect fit between the binding pocket and the 3D structure of the ligand greatly benefits the ligand in accessing more amino acids in the binding pocket. Their interaction stability and toxicity show that quercetin 3'-glucoside, quercetin 3,4'-diglucoside, and rutin are potent oxidative stress modulators in treating ROS-induced cancer.
<p>Kipas laut (<em>Gorgonia mariae</em>) telah digunakan masyarakat Maluku secara turun temurun sebagai obat asma. Kandungan metabolit sekunder yang paling dominan dalam kipas laut adalah sterol, dimana memiliki aktivitas terapi melalui efek sinergisme antara senyawa metabolit dengan polivalent activity. Pengujian kipas laut sebagai anti-asma belum pernah dilaporkan sebelumnya. Oleh karena itu, perlu dilakukan virtual screening menggunakan metode in silico pada komponen sterol kipas laut sebagai tahap awal dalam menentukan efektivitas terapi anti-asma dengan memprediksi nilai ikatan energi bebas (ΔG), konstanta inhibisi (Ki), dan interaksi residu asam amino menggunakan Autodock Tools 4.2 dan Discovery Studio 2016 Client®. Keamanan dan efektivitas kandidat obat dievaluasi menggunakan parameter dari Lipinski Rule of Five dan pre-ADMET. Hasil penelitian menunjukkan bahwa konstanta inhibisi dan ikatan energi bebas (Ki; ΔG) dari komponen senyawa kipas laut dapat diurutkan secara potensial yaitu 4,24-dimetil kolestanol (0,809; -12,40) &gt; 24-metil-22-dehidrokolesterol (0,864; -12,36) &gt; 23-demetil gorgosterol (1,74; -11,95) &gt; 4,24-dimetil-22-dehidrokolestanol (1,89; -11,90). Residu asam amino yang berperan penting dalam aktivitas inhibisi hCHIT1 adalah 213-ASP. Semua komponen senyawa uji memiliki nilai log P lebih dari 5 yang menunjukkan bahwa kelarutan dan toksisitas perlu diperhatikan. Evaluasi distribusi pre-ADMET berdasarkan nilai dari pengikatan protein plasma menunjukan bahwa senyawa uji dapat berdifusi menembus membran plasma dan berinteraksi sesuai target farmakologi. Selain itu, hasil parameter uji toksisitas menunjukkan bahwa senyawa 23-demetil gorgosterol dan 4,24-dimetil-22-dehidrokolestanol memiliki potensi sebagai anti-asma.</p><p><strong>Virtual Screening of the Compounds in Gorgonians </strong><strong>(<em>Gorgonia mariae</em>) as anti-asthma. </strong>The people of Maluku have used Kipas laut (G. mariae) for generations as an asthma medicine. The secondary metabolite that is most dominant in kipas laut is sterols, which have therapeutic activity through the synergistic effect between metabolite compounds and polyvalent activity. Anti-asthma activity of kipas laut has never been reported. Therefore, it is necessary to do virtual screening using the in silico method on the sterol component of kipas laut as a first step in determining the effectiveness of anti-asthma therapy by predicting the value of free energy bonds (ΔG), constant inhibition (K<sub>i</sub>), and interactions of amino acid residues using Autodock Tools 4.2 and Discovery Studio 2016 Client®. The effectiveness and safety of prospective drugs are evaluated using the Lipinski Rule of Five and pre-ADMET. The results showed that the value of inhibition constants and free energy bonds (Ki; ΔG) on the compound of kipas laut that was potentially sorted was 4.24-dimethyl cholestanol (0.809; -12.40) &gt; 24-methyl-22-dehydrocholesterol (0.864; -12.36) &gt; 23-demethyl gorgosterol (1.74; -11.95) &gt; 4.24-dimethyl-22-dehidrokolestanol (1.89; -11.90). The crucial residues of amino acids is 213-ASP, which play a significant role in hCHIT1 inhibitory activity. All components of the test compound have a log P value of more than five, which indicates that solubility and toxicity need to be considered. Evaluation of the pre-ADMET based on the value of plasma protein binding shows that the test compound can diffuse through the plasma membrane and interact according to pharmacological targets. In addition, the results of the toxicity test showed that 23-demethyl gorgosterol and 4.24-dimethyl-22-dehidrokolestanol compounds have potential as anti-asthma.</p>
Buah Merah, a typical fruit from Papua, Indonesia which is used empirically in cancer therapy is rich in carotenoids and flavonoids. However, the mechanisms by which Buah Merah ameliorates cancer remained unknown. Natural antioxidant enzymes and pro-oxidant enzymes modulation significantly suppressed ROS production and cancer growth. Therefore, the determination of target enzymes of Buah Merah contents was studied through an in silico approach. Carotenoid and flavonoid compounds from Buah Merah were docked to 7 ROS modulating enzymes using Autodock Vina and the interaction stability was studied using the CABS Flex 2.0 server. The crucial amino acids of each enzyme were determined using DockFlin and prediction of acute oral toxicity of each test ligand was studied using ProTox-II. Based on the molecular docking results, quercetin 3'-glucoside is the most potent compound in binding to CAT, GR, GPx, SOD, LOX, and NOX with binding energy values of -11.2, -9.7, -8.6, -10.2, -10.7, and -12.8 kcal/mol, respectively. Meanwhile, taxifolin 3-O-α-arabinopyranose produced the highest binding affinity of -10.0 kcal/mol at the XO. Each test ligand formed stable interactions with ROS modulating enzymes and formed bonds with crucial amino acids resulting in strong adhesion compared to native and reference ligands. The glucoside group of quercetin 3'-glucoside plays an essential role in determining the proper position in the attachment and supports the formation of hydrogen bonds with receptors. With low acute oral toxicity, it can be concluded that quercetin 3'-glucoside from Buah Merah is a potent oxidative stress modulator in cancer prevention and therapy.
<p><strong>ABSTRAK.</strong> Kipas laut (<em>Gorgonia mariae</em>) telah digunakan masyarakat Maluku secara turun temurun sebagai obat asma. Kandungan metabolit sekunder yang paling dominan dalam kipas laut adalah sterol, dimana memiliki aktivitas terapi melalui efek sinergisme antara senyawa metabolit dengan polivalent activity. Pengujian kipas laut sebagai anti-asma belum pernah dilaporkan sebelumnya. Oleh karena itu, perlu dilakukan virtual screening menggunakan metode in silico pada komponen sterol kipas laut sebagai tahap awal dalam menentukan efektivitas terapi anti-asma dengan memprediksi nilai ikatan energi bebas (ΔG), konstanta inhibisi (Ki), dan interaksi residu asam amino menggunakan Autodock Tools 4.2 dan Discovery Studio 2016 Client®. Keamanan dan efektivitas kandidat obat dievaluasi menggunakan parameter dari Lipinski Rule of Five dan pre-ADMET. Hasil penelitian menunjukkan bahwa konstanta inhibisi dan ikatan energi bebas (Ki; ΔG) dari komponen senyawa kipas laut dapat diurutkan secara potensial yaitu 4,24-dimetil kolestanol (0,809; -12,40) &gt; 24-metil-22-dehidrokolesterol (0,864; -12,36) &gt; 23-demetil gorgosterol (1,74; -11,95) &gt; 4,24-dimetil-22-dehidrokolestanol (1,89; -11,90). Residu asam amino yang berperan penting dalam aktivitas inhibisi hCHIT1 adalah 213-ASP. Semua komponen senyawa uji memiliki nilai log P lebih dari 5 yang menunjukkan bahwa kelarutan dan toksisitas perlu diperhatikan. Evaluasi distribusi pre-ADMET berdasarkan nilai dari pengikatan protein plasma menunjukan bahwa senyawa uji dapat berdifusi menembus membran plasma dan berinteraksi sesuai target farmakologi. Selain itu, hasil parameter uji toksisitas menunjukkan bahwa senyawa 23-demetil gorgosterol dan 4,24-dimetil-22-dehidrokolestanol memiliki potensi sebagai anti-asma.</p><p><strong>ABSTRACT. Virtual Screening of the Compounds in Gorgonians </strong><strong>(<em>Gorgonia mariae</em>) as anti-asthma. </strong>The people of Maluku have used Kipas laut (G. mariae) for generations as an asthma medicine. The secondary metabolite that is most dominant in kipas laut is sterols, which have therapeutic activity through the synergistic effect between metabolite compounds and polyvalent activity. Anti-asthma activity of kipas laut has never been reported. Therefore, it is necessary to do virtual screening using the in silico method on the sterol component of kipas laut as a first step in determining the effectiveness of anti-asthma therapy by predicting the value of free energy bonds (ΔG), constant inhibition (K<sub>i</sub>), and interactions of amino acid residues using Autodock Tools 4.2 and Discovery Studio 2016 Client®. The effectiveness and safety of prospective drugs are evaluated using the Lipinski Rule of Five and pre-ADMET. The results showed that the value of inhibition constants and free energy bonds (Ki; ΔG) on the compound of kipas laut that was potentially sorted was 4.24-dimethyl cholestanol (0.809; -12.40) &gt; 24-methyl-22-dehydrocholesterol (0.864; -12.36) &gt; 23-demethyl gorgosterol (1.74; -11.95) &gt; 4.24-dimethyl-22-dehidrokolestanol (1.89; -11.90). The crucial residues of amino acids is 213-ASP, which play a significant role in hCHIT1 inhibitory activity. All components of the test compound have a log P value of more than five, which indicates that solubility and toxicity need to be considered. Evaluation of the pre-ADMET based on the value of plasma protein binding shows that the test compound can diffuse through the plasma membrane and interact according to pharmacological targets. In addition, the results of the toxicity test showed that 23-demethyl gorgosterol and 4.24-dimethyl-22-dehidrokolestanol compounds have potential as anti-asthma.</p>
Knipholone is an antiplasmodial phytocompound obtained from the roots of <i>Kniphofia foliosa</i>. Despite several available studies, the molecular drug targets of knipholone in <i>P. falciparum</i> remained unknown. Nowadays, <i>in silico</i> techniques are widely used to study the molecular interactions between compounds and proteins as they provide results quickly with high precision and accuracy. In this study, we aim to identify the potential molecular drug targets of knipholone in <i>P. falciparum</i>. We selected 10 proteins of <i>P. falciparum</i> with unique metabolic functions and we found that knipholone showed better binding affinity than the native ligands of 6 proteins. Out of the 6 proteins, knipholone showed better enzyme inhibitory potential than the native ligands of 4 proteins. We carried out a 100 ns MD simulations for knipholone and the native ligands of four proteins and this was followed by binding free energy calculations. In each step, the performance of knipholone was compared to the native ligands of the proteins. Knipholone outperformed the native ligand of Glutathione-S-Transferase (1OKT) at crucial computational studies as evidence from the lower protein-ligand root mean square deviation value, protein root mean square fluctuation value, and protein-ligand binding free energies. The ligand properties of knipholone provide additional evidence for its stability and it maintains adequate protein-ligand contacts during the entire simulation. The density functional theory study also supported the stability of knipholone at the active binding site of 1OKT. From the studied proteins, we conclude that Glutathione-S-Transferase is the most favorable drug target for knipholone in <i>P. falciparum</i>.Communicated by Ramaswamy H. Sarma.
Recombinant hEGF produced by extracellular secretion using <i>E. coli</i> BL21 has optimal diabetic wound healing activity through increased fibroblast proliferation.
Abstract Background Neuroinflammation is a key pathological feature of a wide variety of neurological disorders, including Parkinson’s, multiple sclerosis, Alzheimer’s, and Huntington’s disease. While current treatments for these disorders are primarily symptomatic, there is a growing interest in developing new therapeutics that target the underlying neuroinflammatory processes. Main body Marine invertebrates, such as coral, sea urchins, starfish, sponges, and sea cucumbers, have been found to contain a wide variety of biologically active compounds that have demonstrated potential therapeutic properties. These compounds are known to target various key proteins and pathways in neuroinflammation, including 6-hydroxydopamine (OHDH), caspase-3 and caspase-9, p-Akt, p-ERK, p-P38, acetylcholinesterase (AChE), amyloid-β (Aβ), HSF-1, α-synuclein, cellular prion protein, advanced glycation end products (AGEs), paraquat (PQ), and mitochondria DJ-1. Short conclusion This review focuses on the current state of research on the neuroprotective effects of compounds found in marine invertebrates and the potential therapeutic implications of these findings for treating neuroinflammatory disorders. We also discussed the challenges and limitations of using marine-based compounds as therapeutics, such as sourcing and sustainability concerns, and the need for more preclinical and clinical studies to establish their efficacy and safety. Graphical abstract
The administration of human Epidermal Growth Factor (hEGF) for diabetic ulcer treatment has been known to have high effectiveness because hEGF has mitogenic properties and has been proved to increase epithelial cell proliferation both in vitro and in vivo. However, hEGF in environmental conditions of diabetic ulcers is known to have low stability, so it is necessary to repeat the administration or protect the hEGF using suitable preparation. This study aims to produce a new drug delivery system in the form of chitosan nanoparticle as a therapy for diabetic ulcers. The nanoparticle formulation was carried out by varying hEGF concentrations using the ionic gelation method with sodium tripolyphosphate (Na-TPP) as a crosslinker and Polyethylene glycol (PEG) as a stabilizer. Chitosan-hEGF nanoparticle formed were characterized using particle size analysis, polydispersity index, zeta potential, SEM and TEM, pH, and FTIR to observe the functional groups. Chitosan-hEGF nanoparticle-containing 0.1% chitosan, 0.15% sodium tripolyphosphate (Na-TPP), 2% polyethylene glycol 400 (PEG 400), and 75 ng/mL hEGF has the smallest particle size with an average of 600.6 nm and D90 value of 135.7 nm. Nanoparticle formed were relatively stable with zeta potential reaching +41,29. The results of in vitro testing showed that hEGF 50 ng/mL had an optimal cell viability percentage with a value of 192%.
Identification of lead compounds with the traditional laboratory approach is expensive and time-consuming. Nowadays, in silico techniques have emerged as a promising approach for lead identification. In this study, we aim to develop robust and predictive 2D-QSAR models to identify lead flavonoids by predicting the IC<sub>50</sub> against <i>Plasmodium falciparum</i>. We applied machine learning algorithms (Principal component analysis followed by K-means clustering) and Pearson correlation analysis to select 9 molecular descriptors (MDs) for model building. We selected and validated the three best QSAR models after execution of multiple linear regression (MLR) 100 times with different combinations of MDs. The developed models have fulfilled the five principles for QSAR models as specified by the Organization for Economic Co-operation and Development. The outcome of the study is a reliable and sustainable in silico method of IC<sub>50</sub> (Mean ± SD) prediction that will positively impact the antimalarial drug development process by reducing the money and time required to identify potential antimalarial lead compounds from the class of flavonoids. We also developed a web tool (JazQSAR, https://etflin.com/news/4) to offer an easily accessible platform for the developed QSAR models.
The β-lactamase of <i>Pseudomonas aeruginosa</i> is known to degrade β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems. With the discovery of an extended-spectrum β-lactamase in a clinical isolate of <i>P. aeruginosa</i>, the bacterium has become multi-drug resistant. In this study, we aim to identify new β-lactamase inhibitors by virtually screening a total of 43 phytocompounds from two Indian medicinal plants. In the molecular docking studies, pinocembrin-7-<i>O</i>-β-D-glucopyranoside (P7G) (-9.6 kcal/mol) from <i>Acacia pennata</i> and ellagic acid (EA) (-9.2 kcal/mol) from <i>Bridelia retusa</i> had lower binding energy than moxalactam (-8.4 kcal/mol). P7G and EA formed 5 (<i>Ser62, Asn125, Asn163, Thr209,</i> and <i>Ser230</i>) and 4 (<i>Lys65, Ser123, Asn125,</i> and <i>Glu159</i>) conventional hydrogens bonds with the active site residues. 100 ns MD simulations revealed that moxalactam and P7G (but not EA) were able to form a stable complex. The binding free energy calculations further revealed that P7G (-59.6526 kcal/mol) formed the most stable complex with β-lactamase when compared to moxalactam (-46.5669 kcal/mol) and EA (-28.4505 kcal/mol). The HOMO-LUMO and other DFT parameters support the stability and chemical reactivity of P7G at the active site of β-lactamase. P7G passed all the toxicity tests and bioavailability tests indicating that it possesses drug-likeness. Among the studied compounds, we identified P7G of <i>A. pennata</i> as the most promising phytocompound to combat antibiotic resistance by potentially inhibiting the β-lactamase of <i>P. aeruginosa</i>.Communicated by Ramaswamy H. Sarma.
These results suggest that Kahar method provides reliable equation with complete and efficient solution to hypotonic and hypertonic problems.
Seawater contains many types of minerals that can be used in the health sector as raw materials for medicines and supplements. In Indonesia, one of the biggest mineral salt-producing areas is Pamekasan Madura with a recent record income of 2,768,809.95 tons. The many mineral resources available and the potential development of medicinal raw materials, it is necessary to check the initial physicochemical properties as a source of information for further research. This study aims to analyze the content, and physicochemical properties of concentrated minerals and magnesium isolates from seawater Pamekasan Madura. After analyzed, it was found that the concentrated mineral contained as many as 25 types of minerals and has a viscosity of 15 mPa.s, a specific gravity of 1,318 - 1,330 with a Baume value of 35-36, and pH of 6.1. The highest mineral concentrations are Sodium (32948.8012 mg / L), Magnesium (20685.5644 mg / L), and Calcium (349.7602 mg / L). Mineral concentrations of seawater Pamekasan Madura were found to be greater than the surface waters of Taiwan Yes Mineral. Magnesium isolate has a purity of 10.88%. Based on the result, it can be concluded that seawater Pamekasan Madura is a potential source of raw material for mineral medicines.
AbstractEllagic acid (EA) is an antiplasmodial polyphenol with reported in-vitro activity against Plasmodium falciparum. Studies have reported that EA acts in the late erythrocytic stages of P. falciparum (Pf) when DNA synthesis is taking place. Pf dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) is an important enzyme for DNA synthesis as its inhibition can kill the parasite. As there is no reported study on the molecular interactions between EA and PfDHFR-TS, we aim to study the molecular interactions between EA and PfDHFR-TS (PDB ID: 3DGA) through molecular docking, molecular dynamics (MD) simulations, binding free energy (MM-GBSA) calculations, and density functional theory (DFT) studies. Site-specific and blind docking revealed that EA has a high binding affinity for the active site of PfDHFR-TS. EA formed hydrogen bonds with multiple active site residues. MD simulations for 100 ns revealed that the PfDHFR-TS-EA complex was stable. The average binding free energy of the PfDHFR-TS-EA complex throughout the 100 ns MD simulations was −39.84 kcal/mol. The energy difference (ΔE = 0.04089 eV) obtained from DFT studies indicates the electrical stability and reactivity of EA at the active site of PfDHFR-TS. We conclude that the antiplasmodial activity of EA might be attributed to its ability to potentially bind with PfDHFR-TS.Keywords: Molecular dockingMD simulationMM-GBSAellagic acidPfDHFR-TS AcknowledgmentsJames H. Zothantluanga is thankful to the University Grants Commission and the Ministry of Tribal Affairs, Government of India for providing the UGC-SRF fellowship (Award No: 202122-NFST-MIZ-03095) to support his Ph.D. research project.Author contributionsStudy design: JHZ; Software, analysis, result interpretation: JHZ, AKU, MR; Drafting, figures, and editing: JHZ, WAE, LP, MSB, DT; Supervision, and critical review: AKU, MRDisclosure statementNo potential conflict of interest was reported by the authors.Data availability statementAll the data will be made available upon proper request to the corresponding author.
<i>In-silico</i> techniques offer a fast, accurate, reliable, and economical approach to studying the molecular interactions between compounds and proteins. In this study, our main aim is to use <i>in-silico</i> techniques as a rational approach for the prediction of the molecular drug targets for luteolin against <i>Plasmodium falciparum</i>. Multi-target molecular docking, 100 nanoseconds (ns) molecular dynamics (MD) simulations, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations were carried out for luteolin against dihydrofolate reductase thymidylate synthase (<i>Pf</i>DHFR-TS), dihydroorotate dehydrogenase (<i>Pf</i>DHODH), and falcipain-2. The native ligands of each protein were used as a reference to evaluate the performance of luteolin. Luteolin outperformed the native ligands of all proteins at molecular docking and MD simulations studies. However, in the MM-GBSA calculations, luteolin outperformed the native ligand of only <i>Pf</i>DHFR-TS but not <i>Pf</i>DHODH and falcipain-2. Among the studied proteins, the <i>in-silico</i> approach predicted <i>Pf</i>DHFR-TS as the most favorable drug target for luteolin.Communicated by Ramaswamy H. Sarma.
Molecular modeling and simulations are essential tools in polymer science and engineering, enabling researchers to predict and understand the properties of macromolecules, including their structure, dynamics, thermodynamics, and overall material characteristics. However, one of the key challenges in polymer simulation and modeling lies in the initial topology design, as existing programs often lack the capability to generate all types of polymer forms. In this study, we present PolyFlin, a powerful Python module that addresses this limitation by allowing the generation of a wide range of polymer structures, from simple homopolymers to complex copolymers, including grafts, cyclic, star, dendrimers, and nets. PolyFlin offers a versatile and efficient tool for exploring and creating diverse polymer architectures, facilitating advancements in various fields that require precise polymer modeling and simulation.
Indonesia is a maritime country with abundant seawater mineral content. One of the regions with the highest salt production is Pamekasan Madura. Minerals are known to have many roles and benefits for our bodies, such as regulating fluid balance and metabolism. Therefore, this study aimed to characterize the physicochemical and microbial properties of concentrated minerals obtained through solvent evaporation and salt deposition for ± 60 days. Acute oral toxicity examination was performed as a first step in determining the safety of concentrated minerals to be used as a raw material for drugs. Based on the test results, the concentrated mineral has a clear yellow color, salty taste, and a bit bitter, odorless, with a pH of 6.6 ± 0.21. Concentrated minerals have high mineral content with levels of potassium, sodium, magnesium, boron, and calcium being 44734.1598 ± 12950.4633, 33192.1198 ± 2699.3419, 8738.1388 ± 100.4894, 2092.5715 ± 60.3224, and 276.9704 ± 13.1133 mg/Kg, respectively. The results of microbiological analysis of untreated concentrated minerals (without antimicrobials or sterilization) showed that the total plate count was within limits, including coliform and Salmonella . However, the total mold and yeast levels exceed the threshold. Based on the results of acute oral toxicity testing, the concentrated mineral is practically nontoxic. With high mineral content and low toxicity, it can be concluded that the concentrated minerals from Pamekasan Madura seawater is potential to be used as a raw medicinal material.
Phytoantioxidants refer to chemicals of plant origin such as flavonoids (flavones, flavonones, flavonols, flavononol, isoflavones, and flavan-3-ols) and other polyphenols (phenolic acids, stilbenes, lignans, and tannins). Phytoantioxidants have been reported to act against parasitic diseases (malaria, dengue, chikungunya, leishmaniasis, Zika virus, and helminth parasites) and neglected tropical diseases (NTDs) (Buruli ulcer, Chagas disease, fascioliasis, human African trypanosomiasis, onchocerciasis, leprosy, lymphatic filariasis, trachoma, and schistosomiasis). However, phytoantioxidants are poorly absorbed in the gut, intestines, and colon. Factors such as food matrix interactions, the extent of liver metabolisms, and intestinal microflora also affect the bioavailability of phytoantioxidants. Due to this, phytoantioxidants have low solubility, bioavailability, bioactivity, and increased toxicity. These issues of phytoantioxidants can be solved with nanoformulations such as nanotransferosomes, nanoemulsions, nanostructured lipid carriers, polylactide nanoparticles, polyurea dendrimer nanoparticles, solid lipid nanoparticles, eudragit-nutriosomes, cyclodextrin-based nanosponge, polymeric nanoparticles, graphene oxide-based nanoformulation, polymeric micelles, nanocrystals, water-soluble copolymer-encapsulated nanoparticle, mesoporous silica nanoparticles, liposomes, liquid crystalline nanoparticles, and zein and hyaluronic acid-based nanoparticles. In this chapter, phytoantioxidants and their nanoformulations, which showed activity against parasitic diseases and NTDs, are highlighted. Several research gaps are identified that will pave the way to develop clinically feasible nanoformulated-phytoantioxidants for the treatment of parasitic diseases and NTDs.
Neglected tropical diseases (NTDs) (Chagas disease, lymphatic filariasis, leprosy, Buruli ulcer, trypanosomiasis, cysticercosis, fascioliasis, dracunculiasis, mycetoma, schistosomiasis, trachoma, and onchocerciasis) burden the low-income or poverty-embedded populations of the tropical region. Many drugs are currently being used to treat parasitic diseases and NTDs. However, drug resistance and toxicity have limited the efficacy of these drugs. An alternative to the traditional drug discovery process is the technique of drug repurposing or repositioning, wherein an existing Food and Drug Administration (FDA)-approved drug used for the treatment of a particular disease was repurposed/repositioned to treat another disease. In this chapter, drug repurposing techniques and computational techniques will be discussed. Specific drugs that have been repurposed for parasitic diseases and NTDs will be covered. Potential leads identified for parasitic diseases and NTDs through computational techniques will also be covered. Many 78existing FDA-approved drugs showed remarkable potential to be repurposed for the treatment of parasitic diseases and NTDs. Different computational techniques such as virtual screening, 3D-QSAR, homology modeling, molecular docking, MD simulations, target fishing, etc. have played a key role in the identification of new compounds for the treatment of parasitic diseases and NTDs.
Identification of lead compounds with the traditional laboratory approach is expensive and time-consuming. Nowadays, in silico techniques have emerged as a promising approach for lead identification. In this study, we aim to develop robust and predictive 2D-QSAR models to identify lead flavonoids by predicting the IC<sub>50</sub> against <i>Plasmodium falciparum</i>. We applied machine learning algorithms (Principal component analysis followed by K-means clustering) and Pearson correlation analysis to select 9 molecular descriptors (MDs) for model building. We selected and validated the three best QSAR models after execution of multiple linear regression (MLR) 100 times with different combinations of MDs. The developed models have fulfilled the five principles for QSAR models as specified by the Organization for Economic Co-operation and Development. The outcome of the study is a reliable and sustainable in silico method of IC<sub>50</sub> (Mean ± SD) prediction that will positively impact the antimalarial drug development process by reducing the money and time required to identify potential antimalarial lead compounds from the class of flavonoids. We also developed a web tool (JazQSAR, https://etflin.com/news/4) to offer an easily accessible platform for the developed QSAR models.
This study investigates the diabetic wound healing potential of M. pendens using an in vivo diabetic animal model and molecular docking targeting MMP, EGF, and FGF pathways. Ethyl acetate hydrogel formulations (0.05%, 0.10%, and 0.15%) were tested over 14 days, with wound closure measured using ImageJ. The fraction contained 91.5 mg QE/g of flavonoids. Docking analysis showed strong binding affinities of quercetin, cholesta-22,24-dien-5-ol, and procyanidin B1 to MMP, EGFR, and FGFR (−8.4 to −10.2 kcal/mol). By day 14, the negative control group showed 30-40% wound closure, while tetrachlorodecaoxide reached 80% (p<0.01). The 0.05% hydrogel achieved 85% closure (p<0.05), and the 0.10% hydrogel showed complete healing (100%, p<0.001). The 0.15% hydrogel was less effective than 0.10%, with significant differences between days 7 and 14 (p<0.05). These findings suggest that M. pendens hydrogel may aid diabetic wound healing through molecular pathway modulation.
I am open to collaborations in drug delivery system (DDS) design integrating laboratory experiments and computational studies. My research …
